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Surface-enhanced Resonance Raman Scattering Nanoprobe Ratiometry for Detecting Microscopic Ovarian Cancer via Folate Receptor Targeting
Published on: March 25, 2019
Selective targeting of metastatic ovarian cancer using an engineered anthrax prodrug activated by membrane-anchored
Nadire Duru1,2, Nisha R Pawar1,2, Erik W Martin1,2
1Center for Vascular and Inflammatory Diseases, University of Maryland School of Medicine, Baltimore, MD 21201.
Abstract:
Treatments for advanced and recurrent ovarian cancer remain a challenge due to a lack of potent, selective, and effective therapeutics. Here, we developed the basis for a transformative anticancer strategy based on anthrax toxin that has been engineered to be selectively activated by the catalytic power of zymogen-activating proteases on the surface of malignant tumor cells to induce cell death. Exposure to the engineered toxin is cytotoxic to ovarian tumor cell lines and ovarian tumor spheroids derived from patient ascites. Preclinical studies demonstrate that toxin treatment induces tumor regression in several in vivo ovarian cancer models, including patient-derived xenografts, without adverse side effects, supportive of progression toward clinical evaluation. These data lay the groundwork for developing therapeutics for treating women with late-stage and recurrent ovarian cancers, utilizing a mechanism distinct from current anticancer therapies.
Insights
Researchers engineered anthrax toxin to selectively kill ovarian cancer cells, offering a novel therapeutic approach for advanced and recurrent disease. This innovative strategy shows promise in preclinical models with no observed adverse effects.
Area of Science:
- Oncology
- Biochemistry
- Drug Development
Background:
- Advanced and recurrent ovarian cancer lack effective treatments.
- Current therapies have limitations in potency and selectivity.
- Novel therapeutic strategies are urgently needed.
Purpose of the Study:
- To develop a novel anticancer strategy for ovarian cancer.
- To engineer anthrax toxin for selective tumor cell activation.
- To evaluate the efficacy and safety of the engineered toxin.
Main Methods:
- Engineered anthrax toxin for selective activation by tumor surface proteases.
- Tested cytotoxicity on ovarian cancer cell lines and patient-derived spheroids.
- Evaluated in vivo efficacy in ovarian cancer models, including patient-derived xenografts.
Main Results:
- Engineered toxin demonstrated selective cytotoxicity against ovarian cancer cells.
- In vivo studies showed significant tumor regression in multiple models.
- No adverse side effects were observed in preclinical evaluations.
Conclusions:
- The engineered anthrax toxin represents a promising, novel therapeutic strategy for ovarian cancer.
- This approach offers a distinct mechanism of action compared to existing therapies.
- Further clinical evaluation is warranted for late-stage and recurrent ovarian cancer.

